Chromosome 11: We have identified an Ashkenazi Jewish pedigree 441, where current lod score with HRAS1/INS is 1.1 (possible linkage). New informative members have been recently located. A newly cloned muscarinic receptor gen (m4) is located in the short arm of 11 by cytogenetic methods. We have identified a polymorphism of m4 with Sst1. Pedigree 441 is informative for this gene, and shows no recombination of m4 with manicdepressive illness of HRAS1/INS, although in combining this with three other pedigrees we have observed 15% recombination with HRAS1/INS. Amish pedigree 110 was not informative on this m4 polymorphism. With an extension of the m4 probe, we have observed a new polymorphism with Rsal, which is segregating in the Amish pedigree. Chromosome 5: A balanced translocation at 5q11 associated with schizophrenia in one family has been reported. A two-allele polymorphism of the glucocorticoid receptor gene (GRL) in that region, has been reported with Bc11. We have studied 3 extended pedigrees with schizophrenia. Using broad diagnostic inclusion criteria, there is a possible linkage. This polymorphism, however, did not distinguish all parental alleles. We have extended the GRL probe using a genomic library in an attempt to increase the linkage information in the 3 extended pedigrees. Another marker, DHFR, reported to be located on 5q11-13, was not linked to GRL or to schizophrenia in these 3 pedigrees. A genetic map of 5q11-13 is being constructed. Color blindness region of X-chromosome: Six new affective disorders pedigrees have been examined using the St-14 polymorphic marker on Xq28 with no evidence of linkage. Neuropharmacological candidate genes: RFLPs were found at beta 1 and beta2 adrenergic receptor gene regions. Linkage to affective disorders was excluded Cloning of genes involved in neurotransmission: 4 clones of protein kinase C substrate (87PKCS) have been isolated from lambda gt11-rat brain cDNA library. Analysis of gene expression by Northern hybridization revealed that one of the cDNAS isolated corresponds to the expected expression of the 87PKCS gene in mouse parent and mutant lymphocyte cell lines. For a second clone, the sequence and pattern of expression is different from the other 2 clones. All clones share sequence homology. A family of substrate proteins amy be present. RFLP resolution: Field inversion gel electrophoresis (FIGE) was found to improve the DNA separation by a factor of 2 for fragments ranging from 23.1 kb to 9.4 kb as well as fragments of 4.4 to 2.0 kb in size.